Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sirolimus is the first of a group of mammalian target of rapamycin inhibitors to be introduced for clinical use in the United States. At the University of Tennessee in Memphis, we have evolved strategies for the use of sirolimus in kidney transplant recipients; which utilize the drug as a primary immunosuppressant and exploit its potential for preserving renal function. Conversions from the calcineurins to sirolimusbased immunosuppression established the efficacy of calcineurin-free immunosuppressants in selected high-risk patients. The conversion experience stimulated the design of protocols for primary use of sirolimus. Posttransplant use of sirolimus was associated with low incidence of rejection whether sirolimus was used with low-dose Prograf or in calcineurin-free protocols. Primary use with full-dose Prograf was associated with a high incidence of calcineurin-related nephrotoxicity and was abandoned in our program. Hematologic and lipid side effects were manageable, as was an observed increase in wound-healing problems and lymphocele formation. Continuous modifications of the sirolimus protocols to increase our benefit-to-risk ratio are ongoing and indicate a continued role for the drug in posttransplant immune suppression.
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PMID:Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients. 1274 77

Rapamune, an inhibitor of the mammalian target of rapamycin, exhibits antiproliferative actions and is increasingly used as adjuvant therapy with calcineurin inhibitors. This study investigated the effect of Rapamune on functional and molecular markers in a rat model of calcineurin inhibitor-induced graft dysfunction. Prograf (6 mg), with or without addition of Rapamune (1 mg), was administered to salt-depleted male rats (n = 6/group). Urinary protein excretion and serum creatinine were measured. Rats were culled at 28 days, and messenger RNA expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was evaluated with reverse transcriptase polymerase chain reaction. Serum creatinine increased with Prograf (P = .01), but not Rapamune (P = .69) treatment, compared to controls at 28 days. The combination of Rapamune and Prograf produced a rise in serum creatinine at 7 (P = .007) and 14 (P = .01) days, but this was not observed at later time points. Urinary protein excretion was unaltered by any drug or combination. While confirming a synergistic effect of Rapamune and calcineurin inhibitors on renal function, these results suggest that sole therapy with Prograf produces inhibition of fibrotic gene expression. Rapamune alone has no deleterious effect on gene expression but addition of Rapamune cancels out the beneficial effects of Prograf.
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PMID:Prograf produces a molecular environment favoring antifibrosis, an effect reversed by the addition of rapamune. 1580 77